Tumor-derived circulating endothelial cell clusters in colorectal cancer

Cima, Igor; Kong, Say Li; Sengupta, Debarka; Tan, Iain Bh; Phyo, Wai Min; Lee, Daniel; Hu, Min; Iliescu, Ciprian; Alexander, Irina; Goh, Wei Lin; Rahmani, Mehran; Suhaimi, Nur-Afidah Mohamed; Vo, Jess Honganh; Tai, Joyce A.; Tan, Joanna H.J.; Chua, Clarinda; Ten, Rachel; Lim, Wan Jun; Chew, Min Hoe; Hauser, Charlotte; Dam, Rob M. van; Lim, Wei-Yen; Prabhakar, Shyam; Lim, Bing; Koh, Poh Koon; Robson, Paul; Ying, Jackie Y.; Hillmer, Axel M.; Tan, Min‐Han

doi:10.1126/scitranslmed.aad7369

Cited by 107 publications

(74 citation statements)

References 41 publications

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“…The presence of ACE on the endothelium of the microvessels within the stroma that also expresses the ESC marker SOX2 is intriguing. This is consistent with recent reports of a primitive endothelial phenotype in close proximity to colorectal tumors (31) suggesting its role in regulating epithelial to mesenchymal transition by influencing angiogenesis (20, 22). However, this remains the topic of further investigation.…”

Section: Discussionsupporting

confidence: 93%

Cancer Stem Cells in Moderately Differentiated Lip Squamous Cell Carcinoma Express Components of the Renin–Angiotensin System

et al. 2017

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AimWe investigated the expression of the renin–angiotensin system (RAS) by cancer stem cell (CSC) subpopulations we have identified in moderately differentiated lip squamous cell carcinoma (MDLSCC).MethodTen MDLSCC samples underwent 3,3-diaminobenzidine (DAB) and immunofluorescent immunohistochemical (IHC) staining for (pro)renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and receptor 2 (ATIIR2). NanoString analysis and Western blotting (WB) were performed on six MDLSCC samples for gene and protein expression, respectively.ResultsIHC staining showed expression of PRR, ATIIR1, and ATIIR2 on cells within the tumor nests (TNs) and the stroma. ACE was localized to the microvessels within the stroma. WB detected PRR, ACE, and ATIIR2. NanoString analysis confirmed gene expression of PRR, ACE, and ATIIR1.ConclusionComponents of the RAS: PRR, ATIIR1, and ATIIR2 are expressed on two CSC subpopulations in MDLSCC, one within the TNs and the other within the stroma. The endothelium of the microvessels within the stroma expresses ACE.

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Section: Discussionsupporting

confidence: 93%

Cancer Stem Cells in Moderately Differentiated Lip Squamous Cell Carcinoma Express Components of the Renin–Angiotensin System

et al. 2017

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“…26 Meanwhile, circulating endothelial cells associated with tumor angiogenesis are reported to be present in the peripheral blood and to exhibit malignant cytomorphological features as well as epithelial and mesenchymal markers. 27 For these reasons, it is important to determine the malignancy, organ-of-origin, and drug targets for putative CTCs to distinguish them from benign cells, especially those isolated from patients without clinically detectable tumors such as cancer patients after radical surgery. Utilization of a panel of protein markers is able to achieve this aim.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell, Multiplexed Protein Detection of Rare Tumor Cells Based on a Beads-on-Barcode Antibody Microarray

Liu¹,

Wang²,

Deng³

et al. 2016

Anal. Chem.

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Circulating tumor cells (CTCs) shed from tumor sites and represent the molecular characteristics of the tumor. Besides genetic and transcriptional characterization, it is important to profile a panel of proteins with single-cell precision for resolving CTCs’ phenotype, organ-of-origin, and drug targets. We describe a new technology that enables profiling multiple protein markers of extraordinarily rare tumor cells at the single- cell level. This technology integrates a microchip consisting of 15000 60 pL-sized microwells and a novel beads-on-barcode antibody microarray (BOBarray). The BOBarray allows for multiplexed protein detection by assigning two independent identifiers (bead size and fluorescent color) of the beads to each protein. Four bead sizes (1.75, 3, 4.5, and 6 μm) and three colors (blue, green, and yellow) are utilized to encode up to 12 different proteins. The miniaturized BOBarray can fit an array of 60 pL- sized microwells that isolate single cells for cell lysis and the subsequent detection of protein markers. An enclosed 60 pL-sized microchamber defines a high concentration of proteins released from lysed single cells, leading to single-cell resolution of protein detection. The protein markers assayed in this study include organ-specific markers and drug targets that help to characterize the organ-of-origin and drug targets of isolated rare tumor cells from blood samples. This new approach enables handling a very small number of cells and achieves single-cell, multiplexed protein detection without loss of rare but clinically important tumor cells.

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“…Recently, an interesting observation has been reported that not all hematogenous CTC clusters are malignant, even though these non-malignant populations also originate from primary mass. This CTM subpopulation express both epithelial and mesenchymal markers, much like single CTCs, but phenotypically they are in fact aggregates of endothelial cells, lacked the genetic variability of primary tumor, and were not cancerous (Cima et al, 2016).…”

Section: Metastatic Potential Of Circulating Tumor Microembolimentioning

confidence: 96%

Circulating tumor microemboli: Progress in molecular understanding and enrichment technologies

Umer

Vaidyanathan

Nguyen

et al. 2018

Biotechnology Advances

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Circulating tumor cells (CTCs) and their clusters, also known as circulating tumor microemboli (CTM), have emerged as valuable tool that can provide mechanistic insights into the tumor heterogeneity, clonal evolution, and stochastic events within the metastatic cascade. However, recent investigations have hinted that CTM may not be mere aggregates of tumor cells but cells comprising CTM exhibit distinct phenotypic and molecular characteristics in comparison to single CTCs. Moreover, in many cases CTM demonstrated higher metastatic potential and resistance to apoptosis as compared to their single cell counterparts. Thus, their evaluation and enumeration may provide a new dimension to our understanding of cancer biology and metastatic cancer spread as well as offer novel theranostic biomarkers. Most of the existing technologies for isolation of hematogenous tumor cells largely favor single CTCs, hence there is a need to devise new approaches, or re-configure the existing ones, for specific and efficient CTM isolation. Here we review existing knowledge and insights on CTM biology. Furthermore, a critical commentary on current and emerging trends in CTM enrichment and characterization along with recently developed ex-vivo CTC expansion methodologies is presented with the aim to facilitate researchers to identify further avenues of research and development.

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Tumor-derived circulating endothelial cell clusters in colorectal cancer

Cited by 107 publications

References 41 publications

Cancer Stem Cells in Moderately Differentiated Lip Squamous Cell Carcinoma Express Components of the Renin–Angiotensin System

Cancer Stem Cells in Moderately Differentiated Lip Squamous Cell Carcinoma Express Components of the Renin–Angiotensin System

Single-Cell, Multiplexed Protein Detection of Rare Tumor Cells Based on a Beads-on-Barcode Antibody Microarray

Circulating tumor microemboli: Progress in molecular understanding and enrichment technologies

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